The highest rates of fetal alcohol spectrum disorders (FASD) in the world have been found in these South African (ZA) towns and their surrounding rural areas where comprehensive prevention research has been ongoing for the past four years. Epidemiology research preceded the prevention for a decade and it is also ongoing. Population-based rates of specific FASD diagnoses in the most recent wave already finalized for the prevention community (Wellington IV) were: 94 per 1,000 for fetal alcohol syndrome (FAS), 56 per 1,000 for partial fetal alcohol syndrome (PFAS), and 30 per 1,000 for alcohol-related neuro-developmental deficits (ARND). In another finalized wave of the comparison areas (BRAM I), the rates were even higher: 61, 46, and 30 per 1,000 respectively for FAS, PFAS, and ARND. Rates of FASD have been persistently high in this region, and our clinical team's ability to diagnose the full spectrum for children age 6-20 years is now proficient. Because of the high prevalence of FASD in these communities, and the extensive epidemiology studies ongoing there, prevention and intervention research can be effectively instituted and evaluated for efficacy. Furthermore, new research trials and etiologic research can now be instituted in a systematic, productive, and potent manner for a refined understanding of FASD across the lifespan and to inform basic science. Improved understandings about the specific characteristics and patterns of FASD in these ZA populations have broad implications for public health in most every human population. With this continuation application, we seek to initiate: 1.) early intervention research (developmental and nutritional) for children as young as 24 months of age that may reduce or ameliorate many of the negative effects of prenatal alcohol exposure in an already-identified cohort of children (FASD and controls); 2.) a comparative study of results from alcohol biomarker (EtG and FAEE) tests and self-reported alcohol use in the prenatal period; and 3.) a detailed case control study of maternal nutrition in the prenatal period. We will continue to research the developmental trajectory of FASD from birth to 7 years in the above cohort and recruit a new newborn cohort. Understandings from these younger children will add to data already collected in multiple, other, cross-sectional studies to inform us about FASD from birth to 23 years. All proposed research is both feasible and possible by continuing Institute of Medicine (IOM)-recommended prevention services and efficacy research, targeting especially the selected and indicated levels established and provided by our current team living and working in the communities. Finally, to fully evaluate the net effect of the comprehensive prevention over 9 years, we will repeat linked evaluation (community survey and in-school prevalence studies) to assess any impact the overall prevention model, particular prevention techniques, and participatory research may have had on risk factors for and actual rates of FASD.